Latest Findings

In this case study, a de novo mutation was reported in an EOEE patient who died from SUDEP. The data found help strengthen the association between SCN8A and EOEE and urge the screening for this mutation for early prevention of SUDEP.

Impaired bone and muscle development in young people treated with antiepileptic drugs

September 7th, 2017

A case-controlled study of patients ranging from 5-18 years old was completed to investigate the effects of antiepileptic drugs on bone development in young people. Researchers found that that those taking antiepileptic drugs had an increased prevalence of fractures, with the distal radius being the most common fracture site in this study.

The exact prevalence of comorbidities in pediatric patients is somewhat unknown at this time as comorbidities can be under-diagnosed. This News & Views article provides insight on the importance of early identification and treatment of comorbidities with children with epilepsy.

Effects of the N1768D mutation on the neurons within the medial entorhinal cortex (mEC) were studied in this paper. mEC neurons are known to provide excitatory input to the dentate gyrus and hippocampus and are known to elevate the circuit excitability in animal models with temporal lobe epilepsy. It was found that unlike hippocampal or neocortical neurons, the mEC neurons are hyperexcitable and this increase in excitability precedes the onset of seizures by more than one month.

The ketogenic diet has shown to be successful in reducing seizures in pharmaco-resistant epilepsy patients, however it is highly unpalatable and difficult to follow. A new diet which combines medium-chain fatty acids, polyunsaturated fatty acid, low glycemic index carbohydrates, and a high BCAA/AAA ratio has shown to reduce excitatory drive and produce results similar to the ketogenic diet.

While it is unknown whether SCN8A mutations can lead to skeletal complications, there have been reports of children with SCN8A mutations who also suffer from skeletal fractures. Researchers analyzed skeletal phenotypes of 2-week-old SCN8A-null mice and revealed there was reduced bone mass as compared to control littermates.

A retrospective study was conducted in five Israeli pediatric clinics examining the effect of cannabidiol (CBD) on children with intractable epilepsy. The results showed that CBD had a positive effect on seizure load and also was associated with improvements in behavior, language, communication, motor skills, and sleep. Some adverse events were also reported which included drowsiness, fatigue, gastrointestinal disturbances and irritability. Further clinical trials using CBD are warranted to validate these findings.

Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

April 7th, 2017

Carbamazapine and oxcarbazepine are some of the common choices for the treatment of focal epilepsy. One of the common side-effects from using these drugs is hyponatremia (low sodium levels in the blood). This study collected sodium blood levels of adults taking these drugs and looked at the prevalence for hyponatremia within this cohort.

This article provides a summarized report on the current literature that is available on the potential use of cannabinoids in the treatment of epilepsy. Everything from the definition of epilepsy, the mechanism of seizures, and the anticonvlusive effects of cannabidiol is covered in this review.

Endocannabinoid system stimulation may be potential approach to treatment of epilepsy

March 29th, 2017

The endocannabinoid system consists of certain lipids and their receptors which modulate activity in the nervous system. A study recently conducted at the Russian Academy of Sciences has shown that drug-induced activation of the endocannabinoid system can prevent damage to the hippocampus, which is involved in the progression of epilepsy.

In the past few weeks, the LGS (Lennox-Gasaut Syndrome) Foundation has partnered with the Epilepsy Genetics Initiative (EGI), which is a program of Citizens United for Research in Epilepsy (CURE). The goal of this partnership is to ensure that more individuals with LGS have access to genetic testing and whole exome sequencing, and they are performing a pilot program open to families. More information on how to partake in this free genetic testing can be found in the linked article.

Physicians performed gene therapy on a teen with sickle cell anemia by genetically altering his bone marrow to compensate for defective DNA. This procedure was successfully done in France, and being the first of its kind, it is unclear whether the procedure will expand to other countries or diseases, though it does show potential.

In this case study, a de novo mutation was reported in an EOEE patient who died from SUDEP. The data found help strengthen the association between SCN8A and EOEE and urge the screening for this mutation for early prevention of SUDEP.

Impaired bone and muscle development in young people treated with antiepileptic drugs

September 7th, 2017

A case-controlled study of patients ranging from 5-18 years old was completed to investigate the effects of antiepileptic drugs on bone development in young people. Researchers found that that those taking antiepileptic drugs had an increased prevalence of fractures, with the distal radius being the most common fracture site in this study.

Effects of the N1768D mutation on the neurons within the medial entorhinal cortex (mEC) were studied in this paper. mEC neurons are known to provide excitatory input to the dentate gyrus and hippocampus and are known to elevate the circuit excitability in animal models with temporal lobe epilepsy. It was found that unlike hippocampal or neocortical neurons, the mEC neurons are hyperexcitable and this increase in excitability precedes the onset of seizures by more than one month.

The ketogenic diet has shown to be successful in reducing seizures in pharmaco-resistant epilepsy patients, however it is highly unpalatable and difficult to follow. A new diet which combines medium-chain fatty acids, polyunsaturated fatty acid, low glycemic index carbohydrates, and a high BCAA/AAA ratio has shown to reduce excitatory drive and produce results similar to the ketogenic diet.

While it is unknown whether SCN8A mutations can lead to skeletal complications, there have been reports of children with SCN8A mutations who also suffer from skeletal fractures. Researchers analyzed skeletal phenotypes of 2-week-old SCN8A-null mice and revealed there was reduced bone mass as compared to control littermates.

A retrospective study was conducted in five Israeli pediatric clinics examining the effect of cannabidiol (CBD) on children with intractable epilepsy. The results showed that CBD had a positive effect on seizure load and also was associated with improvements in behavior, language, communication, motor skills, and sleep. Some adverse events were also reported which included drowsiness, fatigue, gastrointestinal disturbances and irritability. Further clinical trials using CBD are warranted to validate these findings.

Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment

February 15th, 2017

This article outlines recent findings in a variety of genetic mutations related to epilepsy, including SCN8A. It summarizes how precision medicine and gene discovery are facilitating rapid progress in the classification of epilepsy, as well as development of medications targeted toward patients with these specific genetic mutations.

Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy

February 13th, 2017

Recent experimentation through mouse models suggests that a N1768D mutation in SCN8A results in hyperexcitability and an elevated persistent sodium current in hippocampal neurons. This data suggests that SCN8A plays a role in neural excitability, which could explain the mechanism through which early infantile epileptic encephalopathy (EIEE) causes severe seizures and cognitive impairment.

De novo mutations in the SCN8A gene are at an increased risk for sudden unexpected death in epilepsy (SUDEP). In this study, the cardiac phenotype of a mouse model expressing the p.Asn1768Asp mutation in Scn8a was investigated for alterations in cardiac excitability. The authors observed prolongation of the early stages of action potential repolarization in mutated myocytes.

The exact prevalence of comorbidities in pediatric patients is somewhat unknown at this time as comorbidities can be under-diagnosed. This News & Views article provides insight on the importance of early identification and treatment of comorbidities with children with epilepsy.

This article outlines the mechanisms through which a mutation in SCN8A results in seizures. Through experimentation in mouse models, researchers have found that decreased SCN8A function in the cortex can lead to convulsive seizure resistance, while decreased SCN8A function in the thalamus can generate absence seizures. The results of this study could motivate future research on the role of SCN8A in other thalamic processes including sleep, attention, and consciousness.

This article summarizes advancements in biotechnology and recent discoveries in epilepsy, which will prospectively be translated into distinct therapy options for the individual patient. These discoveries include the role of inflammatory cell types in the development of epilepsy, the use of intracranial neurostimulation in interrupting seizures, as well as a discussion of the role of bioinformatics in gene identification.

While there are numerous anti-seizure medications on the market (20+), it appears that doctors in the United States have reached a consensus about what medications to prescribe for pediatric patients. Researchers have reported that 63% of patients with a newly diagnosed non-syndromic epilepsy are prescribed levetiracetam as a first choice. Levetiracetam as a first choice is a North American phenomenon, whereas outside the continent, carbazepine and oxcarbazepine are more frequently prescribed.

This article provides a summarized report on the current literature that is available on the potential use of cannabinoids in the treatment of epilepsy. Everything from the definition of epilepsy, the mechanism of seizures, and the anticonvlusive effects of cannabidiol is covered in this review.

Endocannabinoid system stimulation may be potential approach to treatment of epilepsy

March 29th, 2017

The endocannabinoid system consists of certain lipids and their receptors which modulate activity in the nervous system. A study recently conducted at the Russian Academy of Sciences has shown that drug-induced activation of the endocannabinoid system can prevent damage to the hippocampus, which is involved in the progression of epilepsy.

In the past few weeks, the LGS (Lennox-Gasaut Syndrome) Foundation has partnered with the Epilepsy Genetics Initiative (EGI), which is a program of Citizens United for Research in Epilepsy (CURE). The goal of this partnership is to ensure that more individuals with LGS have access to genetic testing and whole exome sequencing, and they are performing a pilot program open to families. More information on how to partake in this free genetic testing can be found in the linked article.

Physicians performed gene therapy on a teen with sickle cell anemia by genetically altering his bone marrow to compensate for defective DNA. This procedure was successfully done in France, and being the first of its kind, it is unclear whether the procedure will expand to other countries or diseases, though it does show potential.

Families of over 150 children globally including Tristan Burk of Stoney Point, Ontario struggle with SCN8A - a rare but devastating genetic disorder - are joining forces to educate the public about SCN8A and inform affected families of available resources.